Neovascularization in Ewing's sarcoma.

Ewing's sarcoma is the second most common bone malignancy in adolescents and young adults after osteosarcoma. Similar to other solid tumors, Ewing's sarcomas require an adequate vascular supply to grow and survive. The development and maintenance of vascular supply is accomplished via three main mechanisms; angiogenesis, vasculogenesis, and tumor cell vasculogenic mimicry. In addition, growth factors, parallel biochemical pathways and the tumor microenvironment are implicated in the initiation and maintenance of neovascularization. This article summarizes the different mechanisms and factors that contribute to neovascularization in Ewing's sarcoma, and discusses the significance of this phenomenon for current treatment options.

Median nerve biodegradable wrapping : Clinical outcome of 10 patients.

Nerve wrap protectors are bioabsorbable synthetic materials made of collagen or extracellular matrix that provide a non-constricting encasement for injured peripheral nerves. They are designed to be used as an interface between the nerve and the surrounding tissue. After hydrated, they transform into a soft, pliable, nonfriable, easy to handle porous conduit. The wall of the nerve wrap has a longitudinal slit that allows to be placed around the injured nerve. Τhis article presents the surgical technique for median nerve neurolysis and nerve coverage using a collagen or an extracellular matrix nerve wrap protector in 10 patients with recurrent or persistent carpal -tunnel syndrome. All patients had a mean of three previous open carpal tunnel operations, which were not successful. The mean follow-up was 3 years. -Under axillary nerve block anaesthesia with the use of -pneumatic tourniquet, a standard open carpal tunnel approach was done incorporating the previous incision. Scar tissue was excised in a healthy bed and the median nerve was thoroughly released with external neurolysis. An appropriate length of nerve wrap protector was cut longitudinally according to the length of nerve release. The nerve wrap was loosely sutured with separate polypropylene sutures No. 7-0. A volar splint was applied for a mean of 2 weeks followed by progressive passive and active range of motion rehabilitation exercises of the wrist and fingers. At the last follow-up, all patients showed improvement of clinical symptoms, static two-point discrimination test and median nerve conduction studies, and absence of Tinel sign. Differences in outcome and complications with respect to the nerve wrap materials used were not observed.

Effect of adjuvant chemotherapy on localized dedifferentiated low-grade osteosarcoma: a systematic review.

PURPOSE: Dedifferentiated low-grade osteosarcomas, which are considered high grade malignancies, can arise from the dedifferentiation of parosteal and low-grade osteosarcomas. Usually, localized dedifferentiated low-grade osteosarcomas are treated by wide resection, and the efficacy of adjuvant chemotherapy is controversial. We conducted a systematic review of studies that investigated the rates of mortality and significant events, such as recurrence and metastases, in localized dedifferentiated low-grade osteosarcoma patients who received wide resection only and in those who received wide resection and (neo-)adjuvant chemotherapy. METHODS: We identified 712 studies through systematic searches of Embase, PubMed, and the Cochrane Central Register of Controlled Trials databases. Of those studies, seven were included in this review and none were randomized controlled trials. In the seven studies, 114 localized dedifferentiated low-grade osteosarcoma patients were examined. RESULTS: Mortality rates of the resection plus chemotherapy (R + C) and the resection only (Ronly) groups were 20.3% and 11.4%, respectively [overall pooled odds ratio, 1.59 (P = 0.662); heterogeneity I2, 0%]. The local recurrence or distant metastasis rate in the R + C group was 36.7% and that in the Ronly group was 28.6% [overall pooled odds ratio, 1.37 (P = 0.484); heterogeneity I2 was 0%]. CONCLUSIONS: Results show a limited efficacy of adjuvant chemotherapy for localized dedifferentiated low-grade osteosarcoma. However, because this was a systematic review of retrospective studies that examined a small number of patients, future randomized controlled trials are needed.

Embolisation of bone metastases from renal cancer.

PURPOSE: This study was done to evaluate embolisation for palliative and/or adjuvant treatment of bone metastases from renal cell carcinoma and discuss the clinical and imaging results. MATERIALS AND METHODS: We retrospectively studied 107 patients with bone metastases from renal cell carcinoma treated from December 2002 to January 2011 with 163 embolisations using N-2-butyl cyanoacrylate (NBCA). Mean tumour diameter before embolisation was 8.8 cm and mean follow-up 4 years. Clinical and imaging effects of treatment were evaluated at follow-up examinations with a pain score scale, analgesic use, hypoattenuating areas, tumour size and ossification. RESULTS: A clinical response was achieved in 157 (96%) and no response in six embolisations of sacroiliac metastases. Mean duration of clinical response was 10 (range 1-12) months. Hypoattenuating areas resembling tumour necrosis were observed in all patients. Variable ossification appeared in 41 patients. Mean maximal tumour diameter after embolisation was 4.0 cm. One patient had intraprocedural tear of the left L3 artery and iliopsoas haemorrhage and was treated with occlusion of the bleeding vessel with NBCA. All patients had variable ischaemic pain that recovered completely within 2-4 days. Postembolisation syndrome was diagnosed after 15 embolisations (9.2%). Transient paraesthesias in the lower extremities were observed after 25 embolisations (25%) of pelvis and sacrum metastatic lesions. CONCLUSIONS: Embolisation with NBCA is recommended as primary or palliative treatment of bone metastases from renal cell carcinoma. Strict adherence to the principles of transcatheter embolisation is important to avoid complications.

Palliative embolisation for advanced bone sarcomas.

PURPOSE: Managing patients with advanced bone sarcomas - namely, recurrent, unresectable and metastatic - is mostly aimed at palliation. The role of embolisation for pain relief for these patients has not been previously reported. We therefore performed this study to emphasise the palliative role of embolisation for pain relief of advanced bone sarcoma patients. MATERIALS AND METHODS: We retrospectively studied 43 patients with advanced bone sarcomas treated with palliative embolisation with N-2-butyl-cyanoacrylate from 2004 to 2011. All patients had primary treatments including chemotherapy, radiation therapy, radiofrequency thermal ablation, and/or surgery for their advanced sarcomas and were referred for embolisation as end-stage treatment for continuous severe local pain. The effect of embolisation was evaluated with a pain score scale and analgesic use. Mean follow-up was 7 (range, 1-19) months); all patients were dead at the last follow-up. RESULTS: In all patients, angiography showed increased pathological vascularisation of the sarcomas; three to six feeding vessels were embolised in each procedure. Almost complete pain relief and >50% reduction in analgesic use was experienced by 36 patients with highly hypervascular sarcomas and sarcomas in the pelvis and shoulder girdle. Moderate pain relief and 50% reduction in analgesic use was experienced by seven patients with spinal and sacral lesions. Within the available follow-up, no patient had recurrent pain with the same intensity as before embolisation. All patients experienced ischaemic pain at the site of embolisation that resolved completely with analgesics. Six patients with advanced pelvic bone sarcomas experienced paraesthesias at the distribution of the sciatic nerve that resolved completely with methylprednisolone. CONCLUSIONS: Embolisation is a safe and effective local palliative treatment for patients with advanced sarcomas, providing optimum pain relief with the least discomfort and the possibility of minor complications only.

Cemented versus cementless endoprostheses for lower limb salvage surgery.

PURPOSE: To determine the survival and failures of cemented vs cementless endoprostheses. METHODS: We retrospectively studied 232 patients treated with lower limb salvage surgery and reconstruction using cementless and cemented endoprostheses from 2002 to 2007. We compared survival and failures of the endoprostheses regarding age, gender, body mass index (BMI), diagnosis, site of reconstruction, radiation therapy, chemotherapy, and stem fixation. RESULTS: The mean patient follow-up was 28 months (median 24; range 12-84). The overall survival of cemented and cementless endoprostheses at 60 months was 64 and 78%, respectively (p=0.0078). Survival at 60 months of cemented and cementless endoprostheses to infection was 68 and 82%, respectively (p=0.0248). Survival of cemented and cementless endoprostheses to aseptic loosening at 60 months was 94 and 96%, respectively (p=0.1493). The only significant univariate and multivariate predictor of survival was the cementless type of stem fixation. CONCLUSION: Cementless endoprostheses have higher overall survival and survival to infection compared to cemented endoprostheses. Survival to aseptic loosening is not different. Stem fixation is the only significant variable for survival.

Clinical outcomes of medical treatments for progressive desmoid tumors following active surveillance: a systematic review.

Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71-100%, 78-92%, 67-96%, 84%, 88%, 86%, 89-100%, 90-100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.

Heterotopic ossification following traumatic brain injury and spinal cord injury: insight into the etiology and pathophysiology.

Neurogenic heterotopic ossification (HO) is the ectopic formation of lamellar bone in non-osseous tissues following traumatic brain or spinal cord injury. The associated complications affect greatly their quality of life. This fact has shifted the focus of scientific effort towards the investigation and understanding of related risk factors and the pathophysiological mechanisms. Recent advancements include the investigation for genetic predisposition and association various biomarkers. In the present article we will analyze the current concepts on this topic, based on clinical and physiological evidence and we will discuss the potential areas for future research on this field.

Tumours of the atlas and axis: a 37-year experience with diagnosis and management.

PURPOSE: This paper presents a single institution's longterm experience regarding the incidence and management of tumours of the atlas and axis and discusses clinical and imaging findings and treatment options. MATERIALS AND METHODS: We searched the registry of the Istituto Ortopedico Rizzoli for patients admitted and treated for tumours of the upper cervical spine. We identified 62 patients over 37 years, from July 1973 to October 2010. There were 39 male and 23 female patients, with a mean age of 39.5 (range 5-77) years. For each patient, we collected data on clinical presentation, imaging and treatment. Mean follow-up was 10 years. RESULTS: Benign bone tumours were diagnosed in 24 (39%) and malignant tumours in 38 (61%) patients. The most common tumours were bone metastases, followed by osteoid osteomas and chordomas. The atlas was involved in six and the axis in 52 patients; in four patients, both the atlas and axis were involved. The most common clinical presentation was pain, torticollis, dysphagia and neurological deficits. Surgical treatment was performed in 35 patients and conservative treatment, including intralesional methylprednisolone injections and halo-vest immobilisation with or without radiation therapy, chemotherapy or embolisation, in the remaining patients. One patient with osteoblastoma of the atlas had local recurrence. All patients with metastatic bone disease had local recurrence; four of the eight patients with plasmacytoma progressed to multiple myeloma within 1-4 years. All patients with chordomas had two to four local recurrences. Patients with osteosarcomas and chondrosarcoma died owing to local and distant disease progression. CONCLUSIONS: Bone tumours of the cervical spine are rare. However, they should be kept in mind when examining patients with neck pain or neurological symptoms at the extremities. In most cases, only intralesional surgery can be administered. Combined radiation therapy and chemotherapy is indicated for certain tumour histologies.

Effect of two sitting postures on lumbar sagittal alignment and intervertebral discs in runners.

PURPOSE: We evaluated in vivo changes in lumbar lordosis and intervertebral discs in runners and assessed the relationship between these changes and degenerative disc disease in runners with and without a history of low back pain. MATERIALS AND METHODS: Using open upright magnetic resonance (MR) imaging, we prospectively studied changes in lumbar lordosis and intervertebral discs of 25 elite long-distance runners in two sitting postures (neutral and extended) before and after 1 h of running and compared the results with disc height and dehydration/degeneration. Seventeen of the 25 runners had a history of low back pain. RESULTS: After 1 h of running, mean lordosis in neutral posture reduced by 4°; reduction was significant in runners with a history of low back pain. A significant reduction in mean lordosis in extension was not observed. Mean disc height significantly reduced in both postures, without, however, any statistical significance between runners with and without a history low back pain in any posture. Variable degrees of disc dehydration/degeneration were observed in 23 runners (57 discs), more commonly at L5-S1. A significant difference of disc dehydration/degeneration between runners with and without a history of low back pain was not observed. CONCLUSIONS: Intervertebral discs undergo significant strain after 1 h of running that in the long term may lead to low back pain and degenerative disc disease. Runners, especially those with low back pain and degenerative disc disease, should be evaluated after training to preserve the normal lumbar lordosis.

Palliative treatments for advanced osteosarcoma.

Advances in diagnostic imaging, interventional radiology, chemotherapy and surgery greatly improved the outcome of patients with osteosarcoma, and made limb salvage possible without compromising survival. In these patients, the prognosis is influenced by the site and resectability of the tumor, prior malignancy, and histological response to preoperative chemotherapy. Unfortunately, the progress has not been as significant in the treatment of advanced osteosarcoma, namely metastatic, recurrent and unresectable tumor. Yet, although advanced and forecasting a dismal prognosis, advanced osteosarcoma is not necessarily untreatable. Aggressive local and medical treatments, including surgical removal of primary and/or metastatic disease are currently available; however, yet, most treatments aim at palliation. Palliative local treatments including isolated limb perfusion, radiation therapy, embolization, chemoembolization, thermal ablation and cryoablation, all have an important role for these patients. The aim of palliative treatments is to achieve a mild response by offering the least discomfort to the patient with the minimum possible complications, and possibly increase of survival.

Expandable tumor prostheses in children.

Any surgical resection in the lower extremities in children will cause a leg length discrepancy from physeal resection. To avoid the resulting functional deficit, leg length discrepancy must be reconciled with surgical techniques to approximate equal leg lengths at skeletal maturity. Currently there are several manufacturers who offer options for prosthetic reconstruction with expandable implants. These implants can be expanded to a length projected on the basis of three factors: the length of bone resected, the anticipated future growth of the contralateral extremity, and the estimated discrepancy of limb length at skeletal maturity. In this article, we review the basic principles and guidelines for prediction of remaining bone growth and planning lengthening in children, and present the currently available expandable prostheses and the evolution performed over time.

Embolisation for vascular injuries complicating elective orthopaedic surgery.

OBJECTIVES: The study aims to present the indications and emphasise the role of embolisation for vascular injuries in orthopaedic surgery. METHODS: Thirty-one patients with vascular injuries complicating elective orthopaedic surgery had embolisation from 2003 to 2010. N-2-butyl cyano-acrylate (NBCA) was used as embolic agent in 28 patients, gelatin sponge in three and coil embolisation in addition to NBCA or gelatin sponge in two patients. The mean follow-up period was 37 months (range, 4-96 months). RESULTS: The most common orthopaedic operations associated with vascular injuries amenable to embolisation were hip-joint procedures; and the most common injuries were arterial tears of branch vessels or non-critical axial vessels, most commonly of the superior glutaeal artery. In all cases, angiography showed the bleeding point, and a single embolisation session effectively stopped bleeding. Embolisation-related complications were not observed. CONCLUSIONS: Embolisation should be considered the treatment of choice for vascular injuries of branch vessels or non-critical axial vessels following elective orthopaedic surgery because of the advantages of minimally invasive therapy and the lack of complications.

Selective arterial embolisation for bone tumours: experience of 454 cases.

PURPOSE: The authors present the experience of a single institution with selective arterial embolisation for primary and metastatic bone tumours. MATERIALS AND METHODS: A total of 365 patients were treated with 454 embolisation procedures from December 2002 to April 2010. Embolisation was the primary treatment for benign bone tumours, adjuvant treatment to surgery for benign and malignant bone tumours and palliative treatment for bone sarcomas and metastases. Indications for repeat embolisation included pain or imaging evidence of progressive disease: 105 patients had repeat embolisation at the same location at an interval of 1-3 months; 260 patients had one embolisation, 78 had two and 29 had three or more. In all patients, N-2-butyl cyanoacrylate (NBCA) in 33% lipiodol was the embolic agent used. RESULTS: A total of 419 of the 454 embolisations (93%) were technically successful. In 35 cases, embolisation was not feasible because of poor lesion vascularisation (21 patients with bone metastases and two with aneurysmal bone cysts), origin of the Adamkiewicz artery in the embolisation field (four patients with bone metastases and one with aneurysmal bone cyst), atheromatosis and arteriosclerosis (five patients with bone metastases) and anatomical and technical problems such as small-calibre vessels, many branches and acute vessel angles (two patients with bone metastases). A clinical response was achieved in 406 of the 419 procedures (97%), and no response in 13 procedures in patients with pelvis and sacrum tumours. Complications included postembolisation syndrome in 81 patients (22%), transient paraesthesias in 41 (11%), skin breakdown and subcutaneous necrosis at the shoulder and pelvis in five (1.4%) and paresis of the sciatic nerve in one (0.3%). CONCLUSIONS: We recommend embolisation as primary or palliative treatment or an adjunct to surgery for tumours of variable histology. Strict adherence to the principles of transcatheter embolisation is important. Arteries feeding the tumour and collaterals must be evaluated carefully and catheterised superselectively to protect the normal tissues. NBCA is considered the most appropriate embolic agent for small-vessel occlusion without major complications.

Fixed versus mobile bearing knee arthroplasty: a review of kinematics and results.

There are several total knee arthroplasty designs available with wide variation in features. The long-term results of total knee replacement with a fixed bearing design have shown a high degree of clinical success. However, implant loosening and polyethylene wear became recognized as long-term causes of late failure. Mobile bearing knee replacements were designed to create a durable surface articulation by using a polyethylene insert that articulates with a metallic femoral component and a metallic tibial tray. The purpose of this article is to review clinical and basic scientific studies comparing the clinical results, the biomechanical features, and the kinematic patterns of fixed versus mobile bearing knee designs. Beside the fact that in vitro kinematic studies have shown reduced polyethylene wear in mobile bearings due to increased implant conformity and reduced polyethylene contact stresses, which should hypothetically prolong polyethylene life, various independent studies for both mobile bearing and fixed bearing prostheses have documented results that are comparable in terms of survival and performance.

Functional and radiographic outcome after tumor limb salvage surgery using STANMORE megaprostheses.

PURPOSE: To report the clinical and radiological outcome of limb salvage surgery with the STANMORE megaprostheses. METHODS: We retrospectively studied 33 patients with musculoskeletal tumor limb salvage surgery using STANMORE megaprostheses. Clinical evaluation was done using the Enneking and the Toronto Extremity Salvage Score (TESS). Radiographic evaluation was done using the International Society of Limb Salvage (ISOLS) score. RESULTS: At a mean follow-up of 18 months, 21 patients were alive with no evidence of disease and two patients were alive with metastatic disease; 9 patients died of metastatic disease and one patient of causes unrelated to the primary tumor. Local recurrence was not observed in any of the patients. The mean Enneking and TESS scores were 76 and 88.4%, respectively. The ISOLS score was excellent or good in 30 cases for bone remodelling, 30 cases for the interface, in 30 cases for anchorage, in 32 cases for the implant body, and in 33 cases for the articulation. Extracortical bone bridging greater than 25% was observed in 8 prostheses. Mechanical survival of the megaprostheses was 97% (32 megaprostheses). Complications included seroma and hematoma formation (12%), skin necrosis and dehiscence at the knee wound (9%), aseptic loosening and infection (6%), quadriceps tendon rupture and peroneal nerve palsy (3%). CONCLUSION: The local recurrence-free survival in this series supports limb salvage surgery. The 97% survival rate of the megaprostheses suggests that the STANMORE modular megaprostheses are valuable for reconstruction of bone defects after tumor resection.

Criteria and outcome of limb salvage surgery.

When sufficient margins of resection surrounding the tumor can be achieved, limb salvage surgery, as opposed to amputation, has become the standard of care in treating patients with bone and soft tissue sarcoma of the extremities. Currently, 90-95% of patients with primary malignant bone and soft-tissue tumors involving the extremities can be treated safely with wide resection and limb salvage surgery with a low risk of recurrence and the same disease-free survival rate as amputative surgery. However, discussions persist regarding the indications and criteria, and whether limb salvage provides superior functional results and quality of life for cancer patients. In this study we aimed to review and update the current criteria, indications and contraindications of limb salvage surgery and discuss its role in the quality of life of cancer patients.

Association of malnutrition with surgical site infection following spinal surgery: systematic review and meta-analysis.

BACKGROUND: Surgical site infection (SSI) following spinal surgery is a frequent clinical problem with significant clinical and socio-economic consequences. Malnutrition has been linked with SSI in various other surgical procedures. AIM: To investigate whether malnutrition is a risk factor for SSI following spinal surgery. METHODS: Two electronic databases (PUBMED and SCOPUS) and the Cochrane Library were searched systematically from inception to May 2019. Cohort and case-control studies assessing malnutrition as a risk factor for SSI in patients undergoing spinal procedures were considered eligible. Μalnutrition was defined according to laboratory measurements or by relevant International Classification of Diseases-9 codes. SSI was the outcome of interest. Two reviewers independently abstracted study data and assessed the risk of bias for each study. Pooled effect estimates were calculated using random effects models. FINDINGS: In total, 22 studies (20 retrospective cohort and two case-control) with over 175,000 participants (of whom 2.14% developed postoperative SSI) were analysed. SSIs were more likely to develop in malnourished patients [odds ratio (OR) 2.31, 95% confidence interval (CI) 1.75-3.05]. While pre-operative malnutrition was significantly associated with SSI in patients undergoing thoracolumbar spinal and sacral surgery, no significant difference was seen in patients undergoing cervical spinal surgery. In subgroup analyses, similar results were observed for both hospital-based (OR 3.16, 95% CI 1.84-5.43) and population-based (OR 2.00, 95% CI 1.63-2.46) studies. CONCLUSIONS: Malnutrition is associated with increased risk of developing SSI after spinal surgery. Further high-quality research is warranted to investigate whether improvement of pre-operative nutritional status can decrease SSI rates.

Biology of implant osseointegration.

Osseointegration refers to a direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant. Currently, an implant is considered as osseointegrated when there is no progressive relative movement between the implant and the bone with which it has direct contact. A direct bone contact as observed histologically may be indicative of the lack of a local or systemic biological response to that surface. It is therefore proposed that osseointegration is not the result of an advantageous biological tissue response but rather the lack of a negative tissue response. The rationale of the present review is to evaluate the basic science work performed on the concept of biology of osseointegration, and to discuss the specific factors as they may relate to osseous healing around an implant.

Adamantinoma of the tibia treated with a new intramedullary diaphyseal segmental defect implant.

In this case report, a 75-year old male presented with a mass on the anterior surface of the mid-shaft of the right tibia. Imaging studies showed a well-circumscribed radiolucent lesion in the anterior tibial cortex, without soft tissue extension. Plain radiographs and computed tomography scan of the chest were negative. Histological diagnosis was consistent with adamantinoma, a rare primary bone tumour. Wide tumour resection of approximately 16 cm of the tibial diaphysis with a surrounding cuff of normal tissue was performed. The bone defect was reconstructed using an intramedullary diaphyseal segmental defect fixation system. At 26 months post-operatively the patient is alive with no evidence of local recurrence, distant metastases or implant failure. The intramedullary diaphyseal segmental defect fixation system is associated with excellent oncological and functional outcomes. Intra-operative modularity, ease of application, immediate post-operative stability and rapid rehabilitation are the major advantages of this diaphyseal prosthesis.